Glycosaminoglycans are a family of polysaccharides formed by the repetition of a uronic acid, glucuronic or iduronic acid, α 1→4 or β 1→3 linked to a hexosamine residue, glucosamine or galactosamine. Hexosamine and uronic acid residues can be variously sulfated. Beside heparin and heparan sulfate, also dermatan sulfate, hyaluronic acid and chondroitin sulfate are included into glycosaminoglycans' family. Physiologically, glycosaminoglycans are organized in proteoglycans, formed by a protein core wherein the glycosaminoglycan is linked by a linkage region. These structures are in charge of the control of biochemical reactions by the uptake and the release of proteins and growth factors (J. F. Kennedy, C. A. White, Bioactive Carbohydrates, 1983, Ellis Horwood Ltd, 211-227).
In particular, chondroitin sulfate is located in cartilages and the epithelia like gastric mucosa or urethelium. In the cartilages it gives elasticity and controls the resistance, while in mucosa and epithelia protects the epithelium itself from the acid aggression in the case of gastric epithelium or by potassium in the case of urethelium. In the pathologies in which the amount of chondroitin sulfate is low such as gastritis or interstitial cystitis the administration of chondroitin sulfate helps to mitigate the inflammation and the correlate damages due to the low chondroitin sulfate content. Extractive chondroitin sulfate normally has an average molecular weight from 10,000 to 50,000 Da. Biosynthetic chondroitin sulfate may be obtained starting from K4 polysaccharide, for example according to the method described in EP 1304338. Its average molecular weight is from 12,000 to 15,000 Da, even though lower or higher molecular weight products may be prepared.
Hyaluronic acid naturally occurs as a regular unsulfated macromolecule formed by a linear disaccharidic sequence of glucuronic acid 1-3 linked to N-acetylglucosamine, while chondroitin sulfate is mainly present in two distinct forms chondroitin-4-sulfate (or ChSA) and chondroitin-6-sulfate (or ChSC). Chondroitin sulfate is formed by disaccharide repetition containing glucuronic acid β1→3 linked to galactosamine that is sulfated or in position 4 or in position 6. Clusters of ChSA and ChSC are present in the same molecule. Occasionally low amount of disulfated and non sulfated disaccharides can be also present within the polysaccharide chain. The proteoglycans containing chondroitin sulfate are formed by a hyaluronic acid backbone onto which protein chains (protein core) bearing branches of condroitin sulfate chains are grafted. A highly viscous macromolecule is thus formed whose viscosity is due to the very high molecular mass and also to the structural characteristics of its components.
Extractive hyaluronic acid has an average molecular weight of the order of 105-106 Da.
Unless otherwise specified, in the present description the term “hyaluronic acid” and “chondroitin sulfate” designates hyaluronic acid and chondroitin sulfate in sodium salt form, the dosages given herein below being referred to sodium hyaluronate and sodium chondroitin sulfate.